title: Cutting edge: Heterosubtypic influenza infection antagonizes elicitation of immunological reactivity to hemagglutinin.
abstract: Influenza-specific immunity in humans is unique because there are repeated exposures to viral strains containing genetically conserved epitopes recruiting memory CD4 T cells and novel epitopes stimulating naive CD4 T cells, possibly resulting in competition between memory and naive lymphocytes. In this study, we evaluated the effect of this competition on CD4 T cell and B cell response specificity using a murine model of sequential influenza infection. We found striking and selective decreases in CD4 T cell reactivity to nonconserved hemagglutinin (HA) epitopes following secondary influenza infection. Surprisingly, this shift in CD4 T cell specificity was associated with dramatic decreases in HA-specific Ab. These results suggest that repeated exposure to influenza viruses and vaccines containing conserved internal proteins may have unintended and negative consequences on the ability to induce HA-specific Ab to novel pandemic strains of influenza. These finding could have important implications on pandemic influenza preparedness strategies.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Nayak
authors.forename: Shabnam
authors.initials: S
authors.lastname: Alam
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Sant
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus